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Hyperhomocysteinemia leads to adverse cardiac remodeling in hypertensive rats
Jacob Joseph1, Abeer Washington, Lija Joseph
1Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock 72205, USA. josephjacob@uams.edu
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Hyperhomocysteinemia (Hhe) worsens cardiac remodeling in hypertensive rats, causing diastolic dysfunction and increased collagen. This study highlights Hhe
Area of Science:
- Cardiovascular Physiology
- Hypertension Research
- Metabolic Disease
Background:
- Hyperhomocysteinemia (Hhe) is epidemiologically linked to cardiovascular disease.
- Hhe may exacerbate cardiac remodeling and dysfunction in hypertension.
- Combined effects of Hhe and hypertension on cardiac and vascular alterations require investigation.
Purpose of the Study:
- To investigate the impact of Hhe on cardiac remodeling and function in spontaneously hypertensive rats.
- To assess the effects of Hhe on myocardial and coronary arteriolar structure and function.
Main Methods:
- Male spontaneously hypertensive rats were fed control, intermediate, or severe Hhe-inducing diets for 10 weeks.
- Cardiac function was assessed in vitro.
- Cardiac and coronary arteriolar remodeling were evaluated using histomorphometry, immunohistochemistry, and biochemical assays.
Main Results:
- Hhe induced diastolic dysfunction, evidenced by altered diastolic pressure-volume curves, without affecting systolic function.
- Perivascular collagen and left ventricular hydroxyproline levels increased with Hhe.
- Coronary arteriolar remodeling, characterized by increased wall thickness due to smooth muscle hyperplasia, and mast cell accumulation were observed.
Conclusions:
- Dietary induction of Hhe for 10 weeks causes significant coronary arteriolar remodeling in hypertensive rats.
- Hhe promotes myocardial collagen deposition and leads to diastolic dysfunction.
- These findings suggest Hhe is a critical factor in adverse cardiac remodeling associated with hypertension.
Abstract:
Hyperhomocysteinemia (Hhe), linked to cardiovascular disease by epidemiological studies, may be an important factor in adverse cardiac remodeling in hypertension. Specifically, convergence of myocardial and vascular alterations promoted by Hhe and hypertension may exacerbate cardiac remodeling and myocardial dysfunction. We studied male spontaneously hypertensive rats fed one of three diets: control, intermediate Hhe inducing, or severe Hhe inducing. After 10 wk of dietary intervention, cardiac function was assessed in vitro, and cardiac and coronary arteriolar remodeling were monitored by histomorphometric, immunohistochemical, and biochemical techniques. Results showed that Hhe induced diastolic dysfunction, as characterized by the diastolic pressure-volume curve, without significant changes in baseline systolic function. Perivascular collagen levels were increased by Hhe, and there was an increase in left ventricular hydroxyproline levels. Myocyte size was not affected. Coronary arteriolar wall thickness increased with Hhe due to smooth muscle hyperplasia. Mast cells increased in parallel with Hhe and collagen accumulation. In summary, 10 wk of Hhe caused coronary arteriolar remodeling, myocardial collagen deposition, and diastolic dysfunction in hypertensive rats.